S Björklund, A Nowacka, D Pham, J Andersson, S Douzane, D Topgaard, J Engblom, K
Thuresson, L Wadsö, H Wennerström, J Bouwstra, E Sparr
The human skin is a large (ca. 2 m2) membrane that separate regions with profoundly different
properties. This implies that several simultaneous transport processes occur across a non-
equilibrium system. The skin is a vital organ, and its outer layer, stratum corneum (SC) forms
the barrier that prevents from desiccation and protects against the uptake of hazardous
chemicals. SC also highly attractive as a target for directed and controlled delivery of drugs.
We aim at a characterization of the material properties of the SC by coupling macroscopic SC
barrier properties to its molecular structure and dynamics. The SC is a sophisticated barrier in
that behaves as a responding membrane, and diffusional transport can be regulated by changes
in the skin environments. One example is the abrupt increase in SC permeability at high
degrees of SC hydration. This penetration enhancement is taken advantage of in transdermal
drug delivery, and it is called "occlusion effect". Through a complementary experimental and
theoretical approach, we have provided a molecular explanation to this effect, and the main
principles are illustrated in the Figure.
Figure: Molecular explanation for occlusion effect in skin: Steady-state flux of a model drug
(metronidazol) across a responding SC membrane (1). The barrier can be switched on and off by varying
the external water gradient. The same behaviour was predicted from a theoretical model for responding
membrane where the water gradient can induce structure changes (2). PT ssNMR studies of intact SC
demonstrated that hydration increase fluidity in SC components (3).
The skin is regularly exposed to osmotic stress due dry and cold climate of the external environment. It is therefore not surprising that osmolytes are naturally present in the skin. In this case, the osmolytes are referred to as the natural moisturizing factor (NMF) and comprise a mixture of e.g. amino acid derivatives, urea and glycerol. We have investigated how osmolytes can act to protect membranes against osmotic stress in model membranes and in intact SC (4). A main conclusion is that both urea and glycerol, which are also common ingredients in skin lotions, increases the molecular mobility of both SC lipids and proteins as well as in lipid model membranes at reduced hydration. In other words, these small polar compounds strongly influence the properties of the apolar components in the membranes. This can be explained by that the polar compounds have low vapor pressure and therefore remain in the membrane system also at reduced RH when water evaporate. This is considered as an important role of NMF in stratum corneum, and it can be related to the effects of osmolytes in other biological
systems under osmotic stress .
References: (1) Björklund, Engblom, Thuresson (2010) J Contr Rel. (2) Sparr & Wennerström
(2001) Biophys J. (3) Björklund, Nowacka, Bouwstra, Sparr, Topgaard (2013) PLoSONE. (4)
Björklund, Andersson, Nowacka, Pham, Topgaard, Sparr. Submitted. (5) Nowacka, Douzane,
Wadsö, Topgaard, Sparr (2012) Soft Matter.


Chemwatch australian msds 26-0813

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